Methods and apparatus to reduce biological carryover using induction heating

ABSTRACT

Methods, systems, apparatus and machine readable media are disclosed to reduce biological carryover. An example method includes generating an alternating electromagnetic field and introducing an aspiration and dispense device into the electromagnetic field. The example method also includes inductively heating the aspiration and dispense device with the electromagnetic field to at least one of denature or deactivate at least one of a protein or a biological entity on a surface of the aspiration and dispense device.

RELATED APPLICATION

This patent claims priority to U.S. application Ser. No. 13/721,931,filed on Dec. 20, 2012, which claims priority to U.S. Provisional PatentApplication Ser. No. 61/580,913, filed on Dec. 28, 2011. Both U.S.application Ser. No. 13/721,931 and U.S. Provisional Patent ApplicationSer. No. 61/580,913 are incorporated herein by reference in theirentireties.

FIELD OF THE DISCLOSURE

This disclosure relates generally to medical diagnostic equipment and,more particularly, to methods and apparatus to reduce biologicalcarryover using induction heating.

BACKGROUND

Probes are used in medical diagnostic equipment to aspirate and/ordispense samples and reagents into/from sample tubes and reactionvessels. The probability of biological carryover or cross contaminationis increased when probes are reused. Some existing methods forpreventing cross contamination of proteins require probes to bereplaced. Probe replacement produces significant waste and increasesoperation costs and time.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of electromagnetic induction.

FIGS. 2A-C illustrate an example aspiration and dispense device beinginductively heated and washed.

FIGS. 3A-E illustrate another example aspiration and dispense devicebeing inductively heated and washed.

FIG. 4 is a schematic illustration of an example architecture for anelectromagnetic field generator.

FIG. 5 is a schematic illustration of another example architecture foran electromagnetic field generator.

FIG. 6 is a schematic illustration of another example architecture foran electromagnetic field generator.

FIG. 7 is a schematic illustration of yet another example architecturefor an electromagnetic field generator.

FIG. 8 is a flow chart representative of an example process that may beperformed to implement example systems disclosed herein.

FIG. 9 illustrates an example processor platform that may be used toimplement any or all of the example methods, systems and/or apparatusdisclosed herein.

DETAILED DESCRIPTION

Automated medical diagnostic equipment and automated pipette systems useone or more aspiration and/or dispense devices such as, for examplepipettes or probes, to aspirate and/or dispense samples such asbiological samples and/or reagents into and/or from reaction vesselssuch as, for example, one or more well(s) on a multi-well plate. Theexterior and interior surfaces of the aspiration and/or dispense devicecome into contact with the sample and/or reagent and a portion of thesample and/or reagent may remain on the exterior and/or interior surfaceafter the sample and/or reagent has been dispensed. Subsequent use ofthe aspiration and/or dispense device could result in sample carryoveror reagent carryover. Such carryover is the transfer of the residualsample and/or reagent to another sample and/or reagent, whichcontaminates the sample and/or reagent and may lead to an inaccurateanalysis or diagnosis.

Some systems include a wash station to wash the surfaces of anaspiration and/or dispense device. However, wash stations requirevolumes of wash solution. In addition, any defects, scratches,indentations or other imperfections or irregularities of the surfaces ofthe aspiration and/or dispense device may harbor biological samplesand/or reagents such that the aspiration and/or dispense device is notsufficiently clean after a washing cycle.

In other systems, electrostatic induction is used to heat an aspirationand/or dispense device to a level of sterilization. Such systems createa non-alternating electrical potential (e.g., a voltage) across theaspiration and/or dispense device and create heat via electricalresistance. These systems require a relatively high voltage and currentand, therefore, have an increased risk of electrical shorting. Inaddition, these systems typically heat the entire aspiration and/ordispense device and, therefore, localized heating and cleaning of only acontaminated region is not possible. Furthermore, the current flows in anon-uniform manner through the aspiration and/or dispense device alongthe paths of least resistance. Areas of the surface of the aspirationand/or dispense device that include defects, scratches, dents or otherirregularities have higher resistance. Therefore, these areas, which areparticularly sensitive to biological buildup, experience less currentflow and, therefore, less heating than other areas of the aspirationand/or dispense device. Thus, devices cleaned through electrostaticinduction may not be sufficiently free from biological carryover.

The example systems, methods and apparatus disclosed herein useelectromagnetic induction heating to clean aspiration and/or dispensedevices. In the examples disclosed herein, reactive proteins and/orother biological entities on the surfaces of the aspiration and/ordispense device are deactivated and/or denatured using heat that isgenerated via electromagnetic induction. The deactivation or denaturingof the biological substances provides protection against biologicalcarryover by reducing or eliminating cross contamination betweendiscrete reactions.

The inductive heating is achieved through a metallic coil, or any othershape of continuous electrically conducting media in which the size andshape and is designed to provide a desired heating pattern, throughwhich a high frequency, high current electrical signal flows to inducean opposing current in a target object (e.g., the aspiration and/ordispense device to be cleaned) per Faraday's law of induction. Theopposing current heats the aspiration and/or dispense device and theresidual proteins and/or other biological matter fixed thereto. Theproteins and/or other biological matter are heated above a criticaltemperature to change the manner in which these materials react and bindto other objects or substances, which reduces the chance for unintendedreactions. The examples disclosed herein reduce or eliminate thelikelihood of contamination between discrete fluid movements orreactions, without the need for extensive washing, expensive coatings orsingle use probes.

An example method disclosed herein includes generating an alternatingelectromagnetic field and introducing an aspiration and/or dispensedevice into the electromagnetic field. The example method also includesinductively heating the aspiration and/or dispense device with theelectromagnetic field to at least one of denature or deactivate at leastone of a protein or a biological entity on a surface of the aspirationand/or dispense device.

Some examples disclosed herein include washing the aspiration and/ordispense device prior to introducing the aspiration and/or dispensedevice into the electromagnetic field. In addition, some examplesinclude washing the aspiration and/or dispense device after inductivelyheating the aspiration and/or dispense device with the electromagneticfield. In some examples, the washing comprises washing with a coolingwash to lower a temperature of the aspiration and/or dispense device.Also, some examples include washing the aspiration and dispense deviceduring inductively heating the aspiration and dispense device with theelectromagnetic field.

Some examples disclosed herein include generating the electromagneticfield by flowing a current through an electrically conducting media,using a frequency that is based on a diameter of the aspiration and/ordispense device. Also, some examples disclosed herein include generatingthe electromagnetic field by flowing a current through an electricallyconducting media, using a frequency that is based on a thickness of askin or wall of the aspiration and/or dispense device. In some examples,the electrically conducting media comprises a coil. In other examples,the electrically conducting media comprises any other shape ofcontinuous electrically conducting media in which the size and shape andis designed to provide a desired heating pattern.

In some of the disclosed examples, the aspiration and/or dispense deviceis raised and/or lowered through the electromagnetic field toinductively heat the aspiration and/or dispense device along a length ofthe aspiration and/or dispense device. Also, in some examples, thethickness of the skin varies along the length of the aspiration and/ordispense device, and the frequency is adjusted as the aspiration and/ordispense device is raised or lowered.

In some examples disclosed herein, only a portion of the aspirationand/or dispense device is inductively heated. In other examples,inductively heating the aspiration and/or dispense device with theelectromagnetic field includes heating the aspiration and/or dispensedevice without directly contacting the aspiration and dispense devicevia an electrical and/or an electrostatic connection.

In some examples, generating the alternating electromagnetic fieldcomprises using a standard electrical wall outlet. Also, some of thedisclosed examples include disposing a wash cup between the aspirationand/or dispense device and an electrically conducting media such as, forexample, a coil used to create the electromagnetic field and preventingdirect contact between the aspiration and dispense device and theelectrically conducting media with the wash cup.

An example system disclosed herein includes an electromagnetic fieldgenerator and an aspiration and/or dispense device to be introduced intothe electromagnetic field and to be inductively heated with theelectromagnetic field. The example system also includes a wash cup tointerpose the electromagnetic field generator and the aspiration anddispense device to prevent direct contact therebetween. In some examplesystems, the aspiration and dispense device lacks an electricalconnector coupled to a surface of the aspiration and dispense device,and the aspiration and dispense device is electrically isolated.

Some example systems also include a washer to wash the aspiration and/ordispense device prior to introducing the aspiration and/or dispensedevice into the electromagnetic field and/or after inductively heatingthe aspiration and/or dispense device with the electromagnetic field. Insome examples, the washer is to wash with a cooling wash to lower atemperature of the aspiration and/or dispense device.

In some examples, the electromagnetic field generator comprises afrequency generator and a coil, and the frequency generator is togenerate a variable frequency current to flow through the coil. Thefrequency is based on a diameter of the aspiration and/or dispensedevice. Also, in some examples, the electromagnetic field generatorcomprises a frequency generator and an electrically conducting media(e.g., a coil or any other shape of continuous electrically conductingmedia in which the size and shape and is designed to provide a desiredheating pattern), and the frequency generator to generate a variablefrequency current to flow through the electrically conducting media. Thefrequency is based on a thickness of a skin of the aspiration and/ordispense device.

Some example systems include an arm to raise or lower the aspiration anddispense device through the electromagnetic field to inductively heatthe aspiration and/or dispense device along a length of the aspirationand dispense device. Some example systems include a frequency generatorto adjust the frequency as the aspiration and/or dispense device israised or lowered. Such frequency may be adjusted where the thickness ofthe skin varies along the length of the aspiration and/or dispensedevice.

In some examples, the electromagnetic field is to inductively heat onlya portion of the aspiration and/or dispense device. In some examples,the aspiration and/or dispense device is to be heated without directlycontacting an electrical connection. In some example systems disclosedherein, a surface of the aspiration and/or dispense device is heated todenature or deactivate at least one of a protein or a biological entityon the surface.

Some example systems include a controller and a feedback loop. Thefeedback loop is to provide data to the controller comprising one ormore of frequency, an impedance, a presence of the aspiration anddispense device in the electromagnetic field, a voltage reading or acurrent reading and the controller to change the frequency to change astrength of the electromagnetic field to vary a heating temperature ofthe aspiration and/or dispense device based on the data.

Also disclosed are example tangible machine readable media havinginstructions stored thereon which, when executed, cause a machine togenerate an alternating electromagnetic field and introduce anaspiration and/or dispense device into the electromagnetic field. Theexample instructions further cause the machine to inductively heat theaspiration and/or dispense device with the electromagnetic field todenature and/or deactivate at least one of a protein or a biologicalentity on a surface of the aspiration and/or dispense device.

Turning now to the figures, FIG. 1 shows a schematic illustration ofelectromagnetic induction. As shown in FIG. 1, a coil 100 includes ahigh frequency alternating (AC) current flowing in a first direction asrepresented by the white arrows. The interior of the loops of the coil100 form a work space 102. When the current is flowing through the coil100, an alternating magnetic field 104 extends through the workspace 102and around the coil 100. A work piece 106, which may represent forexample, a portion of a probe or other aspiration and/or dispensedevice, may be inserted into the workspace 102. The alternating magneticfield 104 produces eddy currents in the work piece 106. The eddycurrents flow in a direction opposite the alternating current in thecoil 100, as represented by the larger arrows. Magnetic hysteresislosses and Ohmic heating raise the temperature of the work piece 106.The heat changes the binding properties of any proteins or otherbiological entities that may be present on surfaces of the work piece106 to denature and deactivate such proteins and biological entities.The foregoing process works with ferrous metals, non-magnetic metals,and/or other conductive materials.

FIGS. 2A-C illustrate a portion of an example system 200 to reducebiological carryover during three operations. The example system 200includes an electromagnetic field generator 202 which, in this example,includes a metal coil 204 such as, for example, a copper coil. The coil204 has a first lead 206 and a second lead 208 to electrically couplethe coil 204 to a power source such as, for example, an AC power source.The interior of the coil 204 forms a workspace into which one or morework piece(s) may be disposed, as described below. As described inconnection with FIG. 1, when an electrical current flows through thecoil 204, a magnetic field is created and an opposing current is inducedin the work piece(s).

The example system 200 also includes an example wash cup 210. In thisexample, the wash cup 210 is an open-ended splash container that may bemade of, for example, glass, ceramic, plastic, electrically insulatingand/or any other suitable non-metallic material. The wash cup 210includes an inlet 212 to enable the introduction of wash fluid into thewash cup 210. The system 200 also includes a pipettor probe or otheraspiration and/or dispense device 214. In this example, the aspirationand/or dispense device 214 is a metal probe such as, for example,stainless steel. In FIG. 2A, the aspiration and/or dispense device 214is above or outside of the coil 204. The aspiration and/or dispensedevice 214 includes a liquid 216, which may be, for example, a sample, areagent a wash solution or any combination thereof. In this example, anexterior surface of the aspiration and/or dispense device 214 iscontaminated with protein or biological matter 218. The protein orbiological matter 218 may be adhered to the exterior surface in ascratch or other surface anomaly and/or due to hydrophobicity, ioniccharges, electrostatic charges, protein adsorption, and/or surfaceenergy.

In FIG. 2B, the aspiration and/or dispense device 214 is lowered intothe wash cup 210, and the coil 204 is powered to generate an alternatingelectromagnetic field. In this example, the wash cup 210 interposes theaspiration and/or dispense device 214 to prevent direct contacttherebetween. Thus, the aspiration and/or dispense device 214 isremotely inductively heated preventing biological contamination with thecoil 204. An advantage to this structure is that a standard aspirationand/or dispense device (e.g., probe) can be used. There is no need foran electrical connector fitted to the aspiration and/or dispense device.Thus, the aspiration and/or dispense device is electrically isolated.The electrical isolation reduces the chances of an operator experiencingan electrical shock because of accidental (or intentional) contact withthe aspiration and/or dispense device. The current generated in theaspiration and/or dispense device occurs only where there is a strongalternating magnetic field, and that current is generated only in thematerial of the aspiration and/or dispense device. More specifically, anoperator does not provide a grounding path for the current beinggenerated in the work piece (e.g., the aspiration and/or dispensedevice) because the current is only being generated within the immediatemagnetic field, and the current is in self-contained and isolated loops.

The electrical current in the coil 204 creates a magnetic field thatinduces an electrical current in the aspiration and/or dispense device214. The electrical current in the aspiration and/or dispense device 214generates heat such that the aspiration and/or dispense device 214 isinductively heated. In this example, the aspiration and/or dispensedevice 214 may be heated to a temperature of, for example 300° C., andany residual proteins and/or biological matter are coagulated, denaturedand deactivated. Temperatures as low as, for example, 43° C. denaturesome proteins. Most proteins incinerate by 300° C. The temperature maybe raised much higher, including, for example, 760° C. If there arescratches or other surface anomalies on the aspiration and/or dispensedevice 214, the current is diverted around the root of the imperfection,which increases the local current density and therefore the local heatgeneration and ensures cleaning of these areas. When there is a crack,scratch, or imperfection, the current is concentrated and directed underthe crack, scratch, or imperfection such that the base experiencesincreased heating, which is where contamination may accumulate. Theliquid 216 may be dispensed from the aspiration and/or dispense device214 prior to or during this operation.

In addition, in the disclosed example, the electromagnetic fieldinductively heats only a portion of the aspiration and/or dispensedevice 214 to increase target cleaning of the aspiration and/or dispensedevice 214 and eliminates the need to heat the entire aspiration and/ordispense device 214. For example, only the portion of the aspirationand/or dispense device 214 located within the work space defined by thecoil 204 is heated. Some example systems include an arm (see FIG. 6) toraise or lower the aspiration and/or dispense device 214 through theelectromagnetic field to inductively heat different portions of theaspiration and/or dispense device 214 along a length of the aspirationand/or dispense device 214.

Also, as described in greater detail below, in some examples, thecurrent flowing through the coil 204 is varied depending on a diameterof the portion of the aspiration and/or dispense device 214 in the workspace and/or depending on a thickness of a skin of the portion of theaspiration and/or dispense device 214 in the work space. In someexamples, the thickness of the skin and/or the diameter varies along thelength of the aspiration and/or dispense device 214 and a frequency ofthe current is adjusted as the aspiration and/or dispense device 214 israised or lowered.

In some examples, there is a pre-treatment procedure such as, forexample, a prewash to clean the surfaces of the aspiration and/ordispense device 214 prior to the entry of the aspiration and/or dispensedevice 214 into the work space of the coil 204. Also, in some examples,there is a post-treatment procedure such as, for example, a postwash asshown in FIG. 2C. In this example, the power to the coil 204 isdeactivated and an active probe wash flushes wash fluid 220 through theinlet 212 to wash the outer surface of the aspiration and/or dispensedevice 214 to remove residue proteins and/or other biological materials.The wash fluid 220 has a relatively cooler temperature to reduce thetemperature of the aspiration and/or dispense device 214 to return thetemperature of the aspiration and/or dispense device to, for example,ambient temperature. The aspiration and/or dispense device 214 is readyto be reused following the operation of FIG. 2B and/or FIG. 2C.

FIGS. 3A-E illustrate another example aspiration and/or dispense device300 being inductively heated and washed. The aspiration and/or dispensedevice 300 is used to transport a sample or reagent 302 (FIG. 3A). Theexterior and interior surfaces of the aspiration and/or dispense device300 include contaminants 304 (FIG. 3B). In some examples, the aspirationand/or dispense device 300 is washed to remove the contaminants 304, andthe aspiration and/or dispense device 300 is placed in the center of acoil 306 (FIG. 3C). The interior of the aspiration and/or dispensedevice 300 may also be cleared, but residual contaminants 308 may remain(FIG. 3D). Though FIGS. 3B-D shows the aspiration and/or dispense device300 in the coil 306 during the pre-wash steps and theaspiration/dispense to clear the device 300, these processes oroperations may occur prior to insertion of the aspiration and/ordispense device 300 in the coil 306.

An alternating current is passed through the coil 306 (FIG. 3D), whichcreates a magnetic field that induces eddy currents in the aspirationand/or dispense device 300. The eddy currents generate heat, asdisclosed above to denature and deactivate any contaminants on and/or inthe aspiration and/or dispense device 300. In some examples a post-washtreatment is provided to remove carbonized proteins 310 (FIG. 3E) orotherwise deactivated and/or unbound proteins 310 that may reside in thefluid channel and/or to cool the aspiration and/or dispense device 300.

FIG. 4 illustrates an example circuit architecture for anelectromagnetic field generator 400 that may be included, for example,in a medical diagnostic system or laboratory automation equipment likean automated pipetting system. The example includes a main power source402. In this example, the main power source 402 is the same power sourcefor the entire medical diagnostic system. Thus, the main power source402 is the same line voltage and frequency as used by the rest of thesystem and as received from a standard wall-mounted electrical outlet.Thus, in this example, there is no dedicated line or high voltage sourceused to power the electromagnetic field generator 400. Instead, the mainpower is a low current, high voltage power. The example generator 400includes a frequency generator 404 that generates the frequency neededto operate the generator 400. In this example, the frequency may be, forexample about 637 kHz. The frequency is adjustable and can be variedbased on the characteristics of an aspiration and/or dispense device orother work piece to be placed in the magnetic field and heated.

In some examples, the frequency also is adjustable based on the type ofreagent and/or sample including, for example, whether the contents ofthe aspiration and/or dispense device was previously a blood sample orwill be a blood sample in a future use. For example, the frequency maybe adjusted based on the amount of bound proteins that is expected for aparticular type of sample. Thus, for example, the frequency/power couldbe reduced for “cleaner solutions” (i.e., solutions with an expectationof a lower amount of bound proteins or other biological carryover). Thesample itself does not impact the rate of or generation of heat in theaspiration and/or dispense device.

In addition, the frequency may also be adjusted if, for example, afuture test is particularly sensitive to carryover. In such examples,the frequency may be adjusted to maximize the heat for reducing and/oreliminating carryover. For example, if an assay has a particularsensitivity to carryover then a higher and/or a maximum available powerand heat generation may be used to reduce and/or eliminate carryover.

Furthermore, in other examples, the frequency may be adjusted to use thelowest effective heat for a particular heating/cleaning cycle to reducematerial stress on the probe, shorten a cycle time and/or maximizeenergy efficiency. In some examples, power usage and/or frequency istailored based on an amount of contaminate aspirated. In such examples,a higher power may be used for a cleaning cycle that involves arelatively larger amount of probe length to be cleaned. Also, in someexamples, a lower power may be used for cleaning a smaller area. In bothof these examples, the time to clean could be consistent even though thepower used and the length of the probe cleaned could be different. Inaddition, in some examples, the time for cleaning and, thus, the time anaspiration and/or dispense device spends heated in the electromagneticfield may be reduced where, for example, a small area of the aspirationand/or dispense device (e.g., probe) is to be cleaned and a relativelyhigher power is used. In some examples, the aspiration and/or dispensedevice does not experience a level of heat near a critical temperatureat which the material of the aspiration and/or dispense device begins toexhibit heat related issues. In addition, control of the frequency and,thus, the heat level, may be used to reduce the material stress,increase the useful life of the aspiration and/or dispense device andmitigate failure. Also, in some examples, when less power in theinduction heater (e.g., in the coil) is desired, the frequency may beincreased with relation to the nominal. This causes less strain onsemiconductor switches (e.g., in the example systems 400, 500, 600, 700disclosed herein) when the driving frequency is higher than the resonantfrequency because the switches are not “hard switching” against apotential.

The example generator 400 also includes a power controller 406 tocontrol the flow of power from the main power source 402 at thefrequency generated by the frequency generator 404. A square wave signalor waveform is used in this example, but other waveforms also may beused including, for example, sinusoidal, triangular or saw toothwaveforms. An example input power may be about 450 Watts.

The example generator 400 also includes a transformer 408. Thetransformer 408 steps down the voltage and increases the current. Thetransformer 408 also provides isolation between a resonant or tankcircuit 410 and the main power 402. The transformer 408 also provides ameans of electrically matching the tank circuit 410 to the main power402 and power controller 406 by magnifying or reducing the impedance ofthe tank circuit 410 as seen by the main power 402 and power controller406 such that excessive current is not drawn by the generator 400. Insome examples, the transformer 408 may have a turns ratio of about5.45:1. Thus, in this example, the current after the transformer 408 isabout 5.45 times larger than the current before the transformer 408, andthe voltage after the transformer 408 is reduced by 5.45 times.

The tank circuit 410 is a parallel inductance-resistance-capacitance(LRC) circuit comprising a resistor 412 (the resistance of the systemincluding transmission wires and the inherent resistance of thefollowing components), an inductor 414 (the inductance of a both a coil416 coupled to the transformer 408 and a work coil 418) and a capacitor420 connected in parallel with a value chosen so that the tank circuit410 resonates at the frequency of the frequency generator 404. Thecapacitor 420 provides the capacitance needed for the resonant circuit,and the work coil 418 provides the inductance and at least some of theresistance in the tank circuit 410. In this example, the capacitor 420is about 0.45 μF in parallel, and the work coil 418 has an inductance ofabout 1.4 μH. The tank circuit 410 further increases the current for thework coil 418. The example work coil 418 operates as disclosed above togenerate an alternating magnetic field which results in an opposingmagnetic field generated by the work piece and therefore raises thesurface temperature of any work piece disposed within a work space 422in the interior of the work coil 418. In this example, thepre-transformer current is about 4.4 A, the post-transformer current isabout 24 A. The tank circuit 410, in this example, increases the currentfurther to about 240 A, resulting in an overall increase of about54.5-fold at the work coil 418. Also, the example work coil 418 mayraise the surface temperature of a work piece such as an aspirationand/or dispense device 0-100° C. in less than one second, 0-300° C. inone to two seconds, and 700-800° C. within seven seconds.

There are several design considerations for optimizing the operation ofthe example generator 400 including, for example, coil design andselection (inductance magnitude, resistance value, small gap between thecoils and the work piece), the component to be heated (physicaldimensions, material composition), the amount of main power available(voltage, current), the desired heating rate, the desired maximumtemperature and the type of heating desired (through heating, surfaceheating). These considerations affect the components used in the examplegenerator 400 including, for example, the nominal frequency generated atthe frequency generator 404 (for heating the work piece), thecapacitance needed (Farad value and kVAR value), the tank circuit 410multiplication value (Q), the phase angle of the tank circuit 410 (φ)(unity power factor at cos(φ)=1), the ratio and location of thetransformer 408, power source design, and connecting wire selection (tominimize stray induction and voltage drop).

Specifically, the frequency to be used for a particular work piecedepends on the desired or physical skin thickness of the work piece, andthe thickness depends on the outer diameter of the work piece assumingbut not limited to a cylindrical cross-section, the wall thickness andthe material composition. The skin thickness is defined as the depthwhere, for example, about 86% of the induced power is generated. Theoptimum depth for a tube or cylindrically-shaped work piece is definedby Equation (1) below.

$\begin{matrix}{3.5 = \frac{t \cdot d}{\delta^{2}}} & {{Eqn}.\mspace{11mu} (1)}\end{matrix}$

In Equation (1), the skin thickness is represented by δ, t=wallthickness (m), and d=tube diameter (m). Equation (1) can be solved forthe skin thickness, which can be used in Equation (2) below to calculatethe frequency, f.

$\begin{matrix}{\delta = \sqrt{\frac{\rho}{\pi \cdot \mu \cdot f}}} & {{Eqn}.\mspace{11mu} (2)}\end{matrix}$

In Equation 2, resistivity is represented by ρ (μΩm) and μ representsthe magnetic permeability (H/m). Equation (2) can be solved to determinethe frequency, f (Hz).

Selection of components for the tank circuit 410 depend on the desiredFrequency f (Hz), the capacitance C (F), and the inductance L (H) asshown below in Equation (3).

$\begin{matrix}{f = \frac{1}{2\pi \sqrt{LC}}} & {{Eqn}.\mspace{11mu} (3)}\end{matrix}$

In addition, the Q factor of the tank circuit 410 may be controlled ormanipulated via the kilo-volt ampere reactive (kVAR), power (W), theangular frequency ω (rad/s), the capacitance C (F), the voltage (V), thecurrent I (A), the resistance R (Ω), inductance L (H) and/or theinductive reactance X_(L) (Ω) as shown below in Equation (4).

$\begin{matrix}{Q = {\frac{{kVA}\; r}{kW} = {\frac{{VA}\; r}{W} = {\frac{\omega \; {CV}^{2}}{I^{2}R} = {\frac{\omega \; L}{R} = \frac{X_{L}}{R}}}}}} & {{Eqn}.\mspace{11mu} (4)}\end{matrix}$

A higher Q value produces a smaller bandwidth, which is more difficultto tune for resonance but provides a higher current multiplication inthe tank circuit 410. Whereas a smaller Q value allows for a largerbandwidth, which is easier to tune for resonance and more resistant tode-tuning but provides a lower current multiplication in the tankcircuit 410. After the components for the tank circuit have beenselected, the impedance Z (Ω) of the circuit may be calculated and theratio of the transformer 408 may be selected for correct matching and tonot draw excessive current from the main power source 402. The impedanceZ_(eq) (Ω) of the tank circuit depends on the angular frequency ω(rad/s), the capacitance C (F), the equivalent series resistance of thecapacitor R_(C) (Ω), the series resistance of the inductor R_(L) (Ω),inductance L (H), equivalent circuit resistance R_(eq) (Ω), andequivalent circuit impedance X_(eq) (Ω), as shown below in Equations(5), (6) and (7).

$\begin{matrix}{Z_{eq} = {{R_{eq} + {j\; X_{eq}}} = {{Z}^{j\phi}}}} & {{Eqn}.\mspace{11mu} (5)} \\{R_{eq} = \frac{{( {{R_{L}R_{C}} + \frac{L}{C}} )( {R_{L} + R_{C}} )} + {( {{\omega \; L\; R_{C}} - \frac{R_{L}}{\omega \; C}} )( {{\omega \; L} - \frac{1}{\omega \; C}} )}}{( {R_{L} + R_{C}} )^{2} + ( {{\omega \; L} - \frac{1}{\omega \; C}} )^{2}}} & {{Eqn}.\mspace{11mu} (6)} \\{X_{eq} = \frac{{( {{\omega \; L\; R_{C}} - \frac{R_{L}}{\omega \; C}} )( {R_{L} + R_{C}} )} - {( {{R_{L}R_{C}} + \frac{L}{C}} )( {{\omega \; L} - \frac{1}{\omega \; C}} )}}{( {R_{L} + R_{C}} )^{2} + ( {{\omega \; L} - \frac{1}{\omega \; C}} )^{2}}} & {{Eqn}.\mspace{11mu} (7)}\end{matrix}$

The optimal transformer ratio Y_(t) depends on the voltage of thesupplied power V_(ps) (V), the maximum current that can be safely drawnfrom the supplied power I_(max) (A), and the impedance of the tankcircuit Z_(eq) (Ω), and the resistance as seen by the power supplyR_(ps) (Ω), as shown below in Equations (8) and (9).

$\begin{matrix}{R_{ps} = {{Z_{eq}Y_{t}^{2}} = \frac{V_{ps}}{I_{\max}}}} & {{Eqn}.\mspace{11mu} (8)} \\{Y_{t} = \sqrt{\frac{V_{ps}}{I_{\max}Z_{eq}}}} & {{Eqn}.\mspace{11mu} (9)}\end{matrix}$

The above equations describe the turn ratio of the transformer 408 thatprovides the maximum amount of power drawn from the power source 402. Ifa ratio larger than the ratio shown in Equation 9 is chosen, the currentdraw from the main power source 402 will be reduced and the overallpower consumption of the generator 400 will decrease.

FIG. 5 illustrates another example circuit architecture for anelectromagnetic field generator 500 that may be included, for example,in a medical diagnostic system or automated pipetting system. Componentsthat are similar to components described in other examples will not berepeated here for this example or for subsequent examples, though thevalues of the components may be different. For example, the currentsource, frequency, capacitor, etc. may have different values but operatein a similar manner as disclosed above. The example generator 500 ofFIG. 5 includes a transformer with a ratio larger than the optimalselection. In this example shown in FIG. 5, a 643 kHz square wave may begenerated by the frequency generator 404. A current source 506, whichincorporates aspects of the main power source 402 and power controller406 of FIG. 4, produces, in this example, a current of about 3.3 A. Thefirst transformer 502 and the second transformer 504 together form, inthis example, a transformer having a turn ratio of about 16:1. Thus, thecurrent multiplication is sixteen times greater after the transformers502, 504. In this example, the post-transformer current is about 52.8 A.The tank circuit 410, in this example, increases the current further toabout 160 A, resulting in an overall increase of about 48-fold at thework coil 418. In this example, the overall system power is reduced, butthe draw on the current source 506 is reduced to match the requirementsdesired in this example.

FIG. 6 illustrates another example circuit architecture for anelectromagnetic field generator 600 that may be included, for example,in a medical diagnostic system or automated pipetting system. Theexample generator 600 of FIG. 6 includes a controller 602 and one ormore feedback loop(s) 604. The feedback loop(s) 604 provide data to thecontroller 602 regarding various metrics of the generator 600 such as,for example, a frequency, an impedance, a temperature, a presence of anaspiration and/or dispense device 606 in the electromagnetic field ofthe work coil 418, a voltage reading and/or a current reading at anypoint in the system. The presence or absence of the aspiration and/ordispense device 606 is detectable through temperature or load changes atthe work coil 418. In addition, a physical characteristic of theaspiration and/or dispense device 606 may change as an arm 608 moves theaspiration and/or dispense device 606 up or down through the work coil418 to change the surface of the aspiration and/or dispense device 606that is disposed in the magnetic field and, therefore, subject toinductive heating. For example, the example aspiration and/or dispensedevice 606 has a smaller diameter (i.e., is tapered) toward a tip 610.The optimal frequency to adequately heat the tip 610 is different thanthe frequency needed to adequately heat a portion of the aspirationand/or dispense device 606 with a larger diameter. Thus, the controller602 may adjust the frequency to change a strength of the electromagneticfield to optimize a heating temperature of the aspiration and/ordispense device 606 based on the data.

The controller 602 also acts as a calibrator to enable the generator 600to self-calibrate based on drifting of the capacitance or impedance overtime. The controller 602 further may also sense shorts and/or otherproblems with the any components of the generator 600 orinterconnections therebetween.

FIG. 7 illustrates another example circuit architecture for anelectromagnetic field generator 700 that may be included, for example,in a medical diagnostic system or automated pipetting system. Theexample generator 700 of FIG. 7 includes a step-up/down transformer 702coupled to the main power 402 and a rectifier 704. The step-up/downtransformer 702 and rectifier 704 are separate components in someexamples and are integrated with the power supply 402 in other examples.The step-up/down transformer 702 and the rectifier 704 enable thegenerator 700 to draw power from the power supply 402 and manipulatethat power into a direct current (DC) signal having a suitable voltageand current capacity. Thus, the generator 700 may be coupled to anelectrical wall outlet in any country and the step-up/down transformer702 and rectifier 704 may be selected and/or adjusted to adjust to thepower available from the electrical outlet in the wall. Thus, thetransformer 702 and/or rectifier 704 may be selected such that thesystem does not draw excessive current from the main power supply 402.In some examples, the step-up/down transformer 702 and the rectifier 704modify the power to change the power supply 402 supplied AC voltage toDC voltage, to have a voltage of 120V and 10 A of current and/orotherwise adjust the supplied power. The example generator 700 alsoinclude additional feedback loops 706 to provide further data to thecontroller 602 such as, for example, current readings, voltage readingsor any other suitable data.

While an example manner of implementing generators 400, 500, 600, 700has been illustrated in FIGS. 4-7, one or more of the elements,processes and/or devices illustrated in FIGS. 4-7 may be combined,divided, re-arranged, omitted, eliminated and/or implemented in anyother way. Further, the example frequency generator 402, powercontroller 406, current source 506, system controller 602, rectifier 704and/or, more generally, the example generators 400, 500, 600, 700 ofFIGS. 4-7 may be implemented by hardware, software, firmware and/or anycombination of hardware, software and/or firmware whether as part of amedical diagnostic device or as a standalone induction heating cleaningdevice. Thus, for example, any of the example frequency generator 402,power controller 406, current source 506, system controller 602,rectifier 704 and/or, more generally, the example generators 400, 500,600, 700 of FIGS. 4-7 could be implemented by one or more circuit(s),programmable processor(s), application specific integrated circuit(s)(ASIC(s)), programmable logic device(s) (PLD(s)) and/or fieldprogrammable logic device(s) (FPLD(s)), etc. When any of the apparatusor system claims of this patent are read to cover a purely softwareand/or firmware implementation, at least one of the example, frequencygenerator 402, power controller 406, current source 506, systemcontroller 602 and/or rectifier 704 are hereby expressly defined toinclude a tangible computer readable medium such as a memory, DVD, CD,Blu-ray, etc. storing the software and/or firmware. Further still, theexample generator 400, 500, 600, 700 of FIGS. 4-7 may include one ormore elements, processes and/or devices in addition to, or instead of,those illustrated in FIGS. 4-7, and/or may include more than one of anyor all of the illustrated elements, processes and devices.

A flowchart representative of an example process that may be used toimplement the apparatus and systems of FIGS. 1-7 is shown in FIG. 8. Inthis example, the process comprises a program for execution by aprocessor such as the processor 912 shown in the example computer 9000discussed below in connection with FIG. 9. The program may be embodiedin software stored on a tangible computer readable medium such as aCD-ROM, a floppy disk, a hard drive, a digital versatile disk (DVD), aBlu-ray disk, or a memory associated with the processor 912, but theentire program and/or parts thereof could alternatively be executed by adevice other than the processor 912 and/or embodied in firmware ordedicated hardware. Further, although the example program is describedwith reference to the flowchart illustrated in FIG. 8, many othermethods of implementing the example systems and apparatus disclosedherein may alternatively be used. For example, the order of execution ofthe blocks may be changed, and/or some of the blocks described may bechanged, eliminated, or combined.

As mentioned above, the example process of FIG. 8 may be implementedusing coded instructions (e.g., computer readable instructions) storedon a tangible computer readable medium such as a hard disk drive, aflash memory, a read-only memory (ROM), a compact disk (CD), a digitalversatile disk (DVD), a cache, a random-access memory (RAM) and/or anyother storage media in which information is stored for any duration(e.g., for extended time periods, permanently, brief instances, fortemporarily buffering, and/or for caching of the information). As usedherein, the term tangible computer readable medium is expressly definedto include any type of computer readable storage and to excludepropagating signals. Additionally or alternatively, the example processof FIG. 8 may be implemented using coded instructions (e.g., computerreadable instructions) stored on a non-transitory computer readablemedium such as a hard disk drive, a flash memory, a read-only memory, acompact disk, a digital versatile disk, a cache, a random-access memoryand/or any other storage media in which information is stored for anyduration (e.g., for extended time periods, permanently, brief instances,for temporarily buffering, and/or for caching of the information). Asused herein, the term non-transitory computer readable medium isexpressly defined to include any type of computer readable medium and toexclude propagating signals. As used herein, when the phrase “at least”is used as the transition term in a preamble of a claim, it isopen-ended in the same manner as the term “comprising” is open ended.Thus, a claim using “at least” as the transition term in its preamblemay include elements in addition to those expressly recited in theclaim.

FIG. 8 illustrates a process 800 of carryover reduction which includes,for example, denaturing and/or deactivating proteins and/or otherbiological materials, sterilization, cleaning, etc. In some examples,the process 800 includes prewashing or otherwise pretreating a probe orother aspiration and/or dispense device (block 802) using, for exampleone or more of the prewashes of FIGS. 2 and 3. The example process 800also includes generating an electromagnetic field (block 804). Anexample electromagnetic field may be generated by, for example, thecoils 100, 204, 306, 418 of FIGS. 1-7 and/or the generators 400, 500,600, 700 of FIGS. 4-7. In some examples, the electromagnetic field is analternating electromagnetic field generated by an AC power supply.

In the example process 800 of FIG. 8, the presence or absence of a probeis detected (block 806). If a probe is not detected, control remains atblock 806 until a probe has been introduced into the generatedelectromagnetic field. When a probe has been introduced into theelectromagnetic field, the example process 800 determines if theelectromagnetic field should be adjusted (block 808). For example, thecontroller 602 may sense that the dimensions of the probe in the workcoil 418 require a different frequency to optimize the electromagneticfield and the resulting induced heat, and the process 800 makes theadjustment (block 810). If no adjustment is necessary or after anadjustment has been made, the process 800 continues, and the probe isheated (block 812). During the heating of the probe (block 812), theposition of the probe may be adjusted (e.g., raised or lowered) withrespect to the electromagnetic field and the coil to change a portion ofthe probe that is subjected to the field and the related inductiveheating. After the desired temperature and/or duration of heating of theprobe to denature and/or deactivate any biological matter, one or moreoptional postwash steps may occur (block 814). For example, a postwashmay rinse the probe of carbonized proteins and/or other residue, acooling wash may lower the temperature of the probe, and/or otherpost-treatments may occur. The example process 800 ends (block 816) andthe probe is reusable.

FIG. 9 is a block diagram of an example computer 900 capable ofexecuting the process of FIG. 8 to implement the apparatus of FIGS. 1-7.The computer 900 can be, for example, a server, a personal computer, orany other type of computing device.

The system 900 of the instant example includes a processor 912. Forexample, the processor 912 can be implemented by one or moremicroprocessors or controllers from any desired family or manufacturer.

The processor 912 includes a local memory 913 (e.g., a cache) and is incommunication with a main memory including a volatile memory 914 and anon-volatile memory 916 via a bus 918. The volatile memory 914 may beimplemented by Synchronous Dynamic Random Access Memory (SDRAM), DynamicRandom Access Memory (DRAM), RAMBUS Dynamic Random Access Memory (RDRAM)and/or any other type of random access memory device. The non-volatilememory 916 may be implemented by flash memory and/or any other desiredtype of memory device. Access to the main memory 914, 916 is controlledby a memory controller.

The computer 900 also includes an interface circuit 920. The interfacecircuit 920 may be implemented by any type of interface standard, suchas an Ethernet interface, a universal serial bus (USB), and/or a PCIexpress interface.

One or more input devices 922 are connected to the interface circuit920. The input device(s) 922 permit a user to enter data and commandsinto the processor 912. The input device(s) can be implemented by, forexample, a keyboard, a mouse, a touchscreen, a track-pad, a trackball,isopoint and/or a voice recognition system.

One or more output devices 924 are also connected to the interfacecircuit 920. The output devices 924 can be implemented, for example, bydisplay devices (e.g., a liquid crystal display, a cathode ray tubedisplay (CRT), a printer and/or speakers). The interface circuit 920,thus, typically includes a graphics driver card.

The interface circuit 920 also includes a communication device such as amodem or network interface card to facilitate exchange of data withexternal computers via a network 926 (e.g., an Ethernet connection, adigital subscriber line (DSL), a telephone line, coaxial cable, acellular telephone system, etc.).

The computer 900 also includes one or more mass storage devices 928 forstoring software and data. Examples of such mass storage devices 928include floppy disk drives, hard drive disks, compact disk drives anddigital versatile disk (DVD) drives.

Coded instructions 932 to implement the process 800 of FIG. 8 may bestored in the mass storage device 928, in the volatile memory 914, inthe non-volatile memory 916, and/or on a removable storage medium suchas a CD or DVD.

From the foregoing, it will appreciated that the above disclosedmethods, apparatus, systems and articles of manufacture can be used toinductively heat aspiration and/or dispense devices in medicaldiagnostic equipment or automated pipetting system. These examplesenable the heating of such aspiration and/or dispense devices withoutrequiring physical or electrical contact with the aspiration and/ordispense device. The risk of an electrical short is reduced, and a lowervoltage may be used. Also, less heat is required to sterilize, denatureor deactivate proteins and other biological matter and/or otherwiseclean the aspiration and/or dispense devices. Thus, the time requiredfor the example processes disclosed herein is also reduced. In addition,the heat is controlled and evenly spread through the targeted surface,and the entire aspiration and/or dispense device does not have to beheated. Also, induction heating of the aspiration and/or dispensedevices enables the devices to be reused. Induction heating producesnegligible solid waste and significantly less biohazardous waste. Theexample systems and apparatus disclosed herein can be plugged into anyelectrical wall outlet and do not require dedicated power supply linesfor the electromagnetic field generators. Induction heating offers asafe, controllable, fast and low incremental cost method for preventingand/or eliminating carryover or cross contamination of proteins and/orother biological matter.

Although certain example methods, apparatus and articles of manufacturehave been described herein, the scope of coverage of this patent is notlimited thereto. On the contrary, this patent covers all methods,apparatus and articles of manufacture fairly falling within the scope ofthe claims of this patent.

What is claimed is:
 1. A method comprising: generating an alternatingelectromagnetic field having a frequency; detecting a characteristic ofan aspiration and dispense device at least partially disposed in theelectromagnetic field; dynamically adjusting the frequency of theelectromagnetic field based on the characteristic to generate a modifiedelectromagnetic field; inductively heating the aspiration and dispensedevice via the modified electromagnetic field to at least one ofdenature or deactivate at least one of a protein or a biological entityon a surface of the aspiration and dispense device.
 2. The method ofclaim 1, wherein the characteristic is a diameter of the aspiration anddispense device.
 3. The method of claim 2, wherein the aspiration anddispense device includes a first portion having a first diameter and asecond portion having a second diameter and further comprisingdynamically adjusting the frequency to generate a first frequency basedon the first diameter when the first portion is disposed in theelectromagnetic field and a second frequency based on the seconddiameter when the second portion is disposed in the electromagneticfield.
 4. The method of claim 1, wherein the characteristic is athickness of a skin of the aspiration and dispense device
 5. The methodof claim 4, wherein the thickness of the skin varies along a length ofthe aspiration and dispense device and further comprising: raising orlowering the aspiration and dispense device to heat the aspiration anddispense device along the length of the aspiration and dispense device;and dynamically adjusting the frequency as the aspiration and dispensedevice is raised or lowered based on the varying thickness of the skin.6. A method comprising: generating an alternating electromagnetic fieldhaving a frequency; introducing an aspiration and dispense device intothe electromagnetic field; identifying a characteristic of theaspiration and dispense device; determining a temperature at which toinductively heat the aspiration and dispense device to at least one ofdenature or deactivate at least one of a protein or a biological entityon a surface of the aspiration and dispense device based on thecharacteristic; adjusting the frequency of the electromagnetic fieldbased on the temperature; and inductively heating the aspiration anddispense device via the electromagnetic field having the adjustedfrequency.
 7. The method of claim 6, wherein the characteristic is asize of an area of the aspiration and dispense device to be inductivelyheated.
 8. The method of claim 7, further comprising adjusting thefrequency to increase the temperature at which the area of theaspiration and dispense device is inductively heated relative to thesize of the area.
 9. The method of claim 7, further comprising adjustingthe frequency to increase the temperature at which a smaller area of theaspiration and dispense device is inductively heated relative to alarger area to reduce an amount of time the aspiration and dispensedevice is in the electromagnetic field.
 10. The method of claim 6,wherein the characteristic is a material stress property of theaspiration and dispense device.
 11. The method of claim 6, furthercomprising adjusting the frequency to inductively heat the aspirationand dispense device at temperature below a temperature at which theaspiration and dispense device exhibits material stress.
 12. The methodof claim 6, wherein identifying the characteristic of the aspiration anddispense device comprises automatically sensing the dimensions of theaspiration and dispense device.
 13. The method of claim 6, whereingenerating an alternating electromagnetic field further comprisesautomatically adjusting at least one of a voltage or a current of powerdrawn from a power source, the power drawn from the power source not toexceed a current limit of the power source.
 14. The method of claim 13,wherein the power source is to be received from a standard electricalwall outlet.
 15. The method of claim 6, further comprising determiningthe temperature at which to inductively heat the aspiration and dispensedevice based on a sensitivity of an assay to contamination carryover forwhich the aspiration and dispense device is to be used and dynamicallyadjusting the frequency based on the determination.
 16. A methodcomprising: generating a variable frequency current via an electricallyconducting media; detecting a presence of an aspiration and dispensedevice relative to the electrically conducting media based on atemperature change or a load change with respect to the electricallyconducting media; dynamically adjusting the variable frequency currentbased on the temperature change or the load change; and inductivelyheating the aspiration and dispense device via the adjusted variablefrequency current to at least one of denature or deactivate at least oneof a protein or a biological entity on a surface of the aspiration anddispense device.
 17. The method of claim 16, further comprisinginductively heating a portion of the aspiration and dispense device. 18.The method of claim 16, further comprising interposing a wash cupbetween the aspiration and dispense device and the electricallyconducting media to prevent direct contact between the aspiration anddispense device and the electrically conducting media.
 19. The method ofclaim 16, further comprising: raising or lowering the aspiration anddispense device to expose at least a portion of the aspiration anddispense device to the electrically conducting media; and dynamicallyadjusting the variable frequency current as the device is raised orlowered.
 20. The method of claim 16, wherein at least one of generatingthe variable frequency current or dynamically adjusting the frequencycurrent is further based on previously collected data with respect oneor more of the variable frequency current or a presence of theaspiration and device relative to the electrically conducting media.